The proposed project is designed to study the interaction of murine leukemia virus (MuLV) with the murine host in relation to the possible outcomes of leukemia or autoimmunity. We plan to concentrate on two particular systems: a) the genetically determined resistance to replication of naturally occurring MuLV's at the murine locus Fv-1; b) a unique restriction of MuLV growth in New Zealand Black (NZB) mice which appears to involve both a replication block and an unusual immunologic response to an endogenous MuLV with the development of autoimmune disease. An effort will be made to further understand the mechanism of the replication block at Fv-1. The genetics of the restriction of MuLV growth in NZB cells will be studied utilizing hybrids of NZB with other mouse strains. A breeding program of AKR X NZB F1 and backcross hybrids will be utilized to determine the effect of NZB-specified markers in interaction with AKR-derived markers for spontaneous induction of MuLV. These interactions will be studied both in regard to the natural history of disease - leukemia and/or autoimmunity, as well as to tissue culture induction of genetically-determined viral expression and replication. It is anticipated that further information will be derived concerning polymorphism of naturally occurring MuLV virions from NZB, AKR and other strains in the course of these studies, utilizing nucleic acid hybridization, radioimmunoassays for MuLV antigens, and virus neutralization tests with well-characterized antisera. It is anticpated that this experimental program will lead to a better understanding of how expression of endogenous MuLV genetic information is controlled in the normal state, and how this control is altered in the development of autoimmunity and neoplasia.